Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis.
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Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. Mutations in COL4A3 and COL4A4 are known to cause Alport syndrome (AS), thin basement membrane nephropathy, and to result in pathognomonic glomerular basement membrane (GBM) findings. Secondary FSGS is known to develop in classic AS at later stages of the disease. Here, we present seven families with rare or novel variants in COL4A3 or COL4A4 (six with single and one with two heterozygous variants) from a cohort of 70 families with a diagnosis of hereditary FSGS. The predominant clinical finding at diagnosis was proteinuria associated with hematuria. In all seven families, there were individuals with nephrotic-range proteinuria with histologic features of FSGS by light microscopy. In one family, electron microscopy showed thin GBM, but four other families had variable findings inconsistent with classical Alport nephritis. There was no recurrence of disease after kidney transplantation. Families with COL4A3 and COL4A4 variants that segregated with disease represent 10% of our cohort. Thus, COL4A3 and COL4A4 variants should be considered in the interpretation of next-generation sequencing data from such patients. Furthermore, this study illustrates the power of molecular genetic diagnostics in the clarification of renal phenotypes.
Collagen Type IV
DNA Mutational Analysis
Glomerular Basement Membrane
Glomerulosclerosis, Focal Segmental
Published Version (Please cite this version)10.1038/ki.2014.305
Publication InfoAdeyemo, AA; Alonso, AS; Cetincelik, U; Conlon, PJ; Gbadegesin, Rasheed Adebayo; Hall, G; ... Wu, G (2014). Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis. Kidney Int, 86(6). pp. 1253-1259. 10.1038/ki.2014.305. Retrieved from http://hdl.handle.net/10161/11616.
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Professor of Pediatrics
Molecular genetics of glomerular disease Genetic risk factors for childhood onset idiopathic nephrotic syndrome
Assistant Professor of Medicine
My lab is interested in understanding how both the renin angiotensin and prostanoid systems regulate blood pressure by altering blood flow to the kidney. My lab utilizes a combination of physiologic and molecular techniques in genetically modified mice to probe questions about how changes in the micro circulation in the kidney alter sodium excretion. The overarching goal of this research is to identify novel mechanisms to target drug therapy for patients with hypertension. My research is fund
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